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@ARTICLE{Lu:178220,
author = {Y. Lu$^*$ and M. Gentiluomo and A. Macauda$^*$ and D.
Gioffreda and M. Gazouli and M. C. Petrone and D. Kelemen
and L. Ginocchi and L. Morelli and K. Papiris and W.
Greenhalf and J. R. Izbicki and V. Kiudelis and B.
Mohelníková-Duchoňová and B. Bueno-de-Mesquita and P.
Vodicka and H. Brenner$^*$ and M. K. Diener and R. Pezzilli
and A. Ivanauskas and R. Salvia and A. Szentesi and M. N.
Aoki and B. C. Németh and C. Sperti and K. Jamroziak and R.
Chammas and M. Oliverius and L. Archibugi and S. Ermini and
J. Novák and J. Kupcinskas and O. Strouhal and P. Souček
and G. M. Cavestro and A. C. Milanetto and G. Vanella and J.
P. Neoptolemos and G. E. Theodoropoulos and H. W. M. van
Laarhoven and A. Mambrini and S. Moz and Z. Kala and M.
Loveček and D. Basso and F. G. Uzunoglu and T. Hackert and
S. G. G. Testoni and V. Hlaváč and A. Andriulli and M.
Lucchesi and F. Tavano and S. Carrara and P. Hegyi and P. G.
Arcidiacono and O. R. Busch and R. T. Lawlor and M. Puzzono
and U. Boggi and F. Guo$^*$ and E. Małecka-Panas and G.
Capurso and S. Landi and R. Talar-Wojnarowska and O. Strobel
and X. Gao$^*$ and Y. Vashist and D. Campa and F.
Canzian$^*$},
title = {{I}dentification of {R}ecessively {I}nherited {G}enetic
{V}ariants {P}otentially {L}inked to {P}ancreatic {C}ancer
{R}isk.},
journal = {Frontiers in oncology},
volume = {11},
issn = {2234-943X},
address = {Lausanne},
publisher = {Frontiers Media},
reportid = {DKFZ-2021-03217},
pages = {771312},
year = {2021},
note = {#EA:C055#LA:C055#},
abstract = {Although 21 pancreatic cancer susceptibility loci have been
identified in individuals of European ancestry through
genome-wide association studies (GWASs), much of the
heritability of pancreatic cancer risk remains unidentified.
A recessive genetic model could be a powerful tool for
identifying additional risk variants. To discover
recessively inherited pancreatic cancer risk loci, we
performed a re-analysis of the largest pancreatic cancer
GWAS, the Pancreatic Cancer Cohort Consortium (PanScan) and
the Pancreatic Cancer Case-Control Consortium (PanC4),
including 8,769 cases and 7,055 controls of European
ancestry. Six single nucleotide polymorphisms (SNPs) showed
associations with pancreatic cancer risk according to a
recessive model of inheritance. We replicated these variants
in 3,212 cases and 3,470 controls collected from the
PANcreatic Disease ReseArch (PANDoRA) consortium. The
results of the meta-analyses confirmed that rs4626538
(7q32.2), rs7008921 (8p23.2) and rs147904962 (17q21.31)
showed specific recessive effects (p<10-5) compared with the
additive effects (p>10-3), although none of the six SNPs
reached the conventional threshold for genome-wide
significance (p < 5×10-8). Additional bioinformatic
analysis explored the functional annotations of the SNPs and
indicated a possible relationship between rs36018702 and
expression of the BCL2L11 and BUB1 genes, which are known to
be involved in pancreatic biology. Our findings, while not
conclusive, indicate the importance of considering
non-additive genetic models when performing GWAS analysis.
The SNPs associated with pancreatic cancer in this study
could be used for further meta-analysis for recessive
association of SNPs and pancreatic cancer risk and might be
a useful addiction to improve the performance of polygenic
risk scores.},
keywords = {genetic polymorphisms (Other) / genome-wide association
study (Other) / pancreatic cancer (Other) / recessive model
(Other) / susceptibility (Other)},
cin = {C055 / C070 / C120 / HD01},
ddc = {610},
cid = {I:(DE-He78)C055-20160331 / I:(DE-He78)C070-20160331 /
I:(DE-He78)C120-20160331 / I:(DE-He78)HD01-20160331},
pnm = {313 - Krebsrisikofaktoren und Prävention (POF4-313)},
pid = {G:(DE-HGF)POF4-313},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:34926279},
pmc = {pmc:PMC8678088},
doi = {10.3389/fonc.2021.771312},
url = {https://inrepo02.dkfz.de/record/178220},
}